Skin cancer is a malignant growth of determined cell types on the skin that may have many causes, though solar radiation is one of the best known. Skin cancer generally develops in the epidermis, the outermost layer of the skin, but can also be located in the dermis. The most common kinds of skin cancer are basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma. Basal cell carcinoma tends to grow slowly and rarely spreads. Squamous cell carcinoma is usually more aggressive than basal cell cancer and is more likely to spread to other parts of the body. The most dangerous kind of skin cancer is melanoma, especially malignant melanoma, which may be fatal if not treated early. Skin cancer is one of the cancers that is growing most rapidly and exceeds in number cases of lung, breast, colo-rectal or prostate cancer.
Transforming growth factor β1 (TGF-β1) is a multi-functional cytokine that regulates a variety of cell processes, such as cell proliferation, differentiation, apoptosis, remodeling of tissue and angiogenesis.
Various experimental models with genetically modified mice (W. Cui et al., “TGFbeta1 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice”, Cell 1996, vol. 86, pp. 531-542), complemented by in vitro studies of cultivated keratinocytes (G. Portella et al., “Transforming growth factor beta is essential for spindle cell conversion of mouse skin carcinoma in vivo: implications for tumor invasion”, Cell. Growth. Differ. 1998, vol. 9, pp. 393-404), suggest that TGF-β1 has a dual function in skin carcinogenesis. It acts both as a suppressor of the carcinogenesis, promoting invasion and metastasis (R. J. Akhurst et al., “Genetic events and the role of TGF beta in epithelial tumour progression”, J. Pathol. 1999, vol. 187, pp. 82-90). Therefore, it is to be expected that the inhibition of this factor in the last stages of carcinogenesis has a suppressor effect on malignant progression, whereas its inhibition at the initial stages of tumor development should have a stimulatory effect on the formation of benign tumors and their progression to malignant carcinoma.
The document WO 00/31135 describes for the first time the P144 peptide (whose INN is disitertide, SEQ ID NO: 1). It also describes how this peptide can be used to treat hepatic diseases, more concretely to treat hepatic fibrosis.
The document WO07048857 describes the use of disitertide as a modulating agent of immune response and in the treatment of cancer. The use of disitertide to treat cancer is in line with the above-mentioned studies, which suggest the stimulatory effect of the factor on malignant progression in the last stages of carcinogenesis.
However, at present there continues to be a need for therapy alternatives that can be applied topically for the prophylactic or therapeutic treatment of skin tumors at early stages, to avoid progression to carcinoma, and that are effective and well tolerated.